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F2rl1  -  coagulation factor II (thrombin) receptor...

Mus musculus

Synonyms: Coagulation factor II receptor-like 1, G-protein coupled receptor 11, Gpcr11, Gpr11, PAR-2, ...
 
 
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Disease relevance of F2rl1

 

High impact information on F2rl1

  • Injections into the paw of sub-inflammatory doses of PAR2 agonists in rats and mice induced a prolonged thermal and mechanical hyperalgesia and elevated spinal Fos protein expression [8].
  • PAR-2 expression, normally limited to endothelial cells in small arterioles, was substantially upregulated 2 weeks after induction of inflammation, both in synovium and in other periarticular tissues [9].
  • Mice heterozygous for PAR-2 gene disruption showed an intermediate phenotype [9].
  • PAR-2 agonists showed potent proinflammatory effects as intra-articular injection of ASKH95, a novel synthetic PAR-2 agonist, induced prolonged joint swelling and synovial hyperemia [9].
  • Given the absence of the chronic inflammatory response in the PAR-2-deficient mice, our findings demonstrate a key role for PAR-2 in mediating chronic inflammation, thereby identifying a novel and important therapeutic target for the management of chronic inflammatory diseases such as rheumatoid arthritis [9].
 

Chemical compound and disease context of F2rl1

 

Biological context of F2rl1

  • Moreover, the accentuated response to PAR-1 activation in PAR-2-deficient mice suggests a compensatory response and potential receptor cross-talk [1].
  • Concomitantly, ERK phosphorylation was seen in DM5/Par2 with the cockroach extract but not with a heat-denatured extract [14].
  • By stable transfection with either an empty vector (DM5/EV) or an expression vector encoding mouse PAR-2 cDNA (DM5/Par2), a pair of lung fibroblast cell lines with or without functional PAR-2 expression were prepared [14].
  • It is well known that PAR-2 participates in the regulation of gastrointestinal motility; however, the results are inconsistent [15].
  • Trypsin, an active form of trypsinogen, regulates cell growth through a G-protein-coupled receptor, the proteinase-activated receptor 2 (PAR-2) [4].
 

Anatomical context of F2rl1

 

Associations of F2rl1 with chemical compounds

  • CONCLUSIONS: Cockroach allergen extract can activate PAR-2 and thereby stimulate mouse lung fibroblasts likely through protease(s) [14].
  • Protective roles for protease-activated receptor-2 (PAR(2)) in the airways including activation of epithelial chloride (Cl(-)) secretion are based on the use of presumably PAR(2)-selective peptide agonists [19].
  • Atropine had no effect on PAR-2 agonist-induced contractions [15].
  • METHODS: Responses to PAR activation using the serine proteases thrombin and trypsin and the peptide agonists for PAR-1 and PAR-2, SFLLRN-NH2 and SLIGRL-NH2, respectively, were investigated in submaximally contracted longitudinal strips of mouse gastric fundus and guinea pig taenia coli [20].
  • Colonic luminal fluid from C. rodentium-infected mice, but not from sham-infected mice, contains active serine proteinases that can activate proteinase-activated receptor-2 (PAR2) [10].
  • Treatment with beta-tryptase resulted in dose-dependent knee joint swelling and synovial vasodilatation in PAR-2(+/+) mice but not PAR-2(-/-) mice [21].
 

Regulatory relationships of F2rl1

 

Other interactions of F2rl1

 

Analytical, diagnostic and therapeutic context of F2rl1

References

  1. Cardiovascular responses mediated by protease-activated receptor-2 (PAR-2) and thrombin receptor (PAR-1) are distinguished in mice deficient in PAR-2 or PAR-1. Damiano, B.P., Cheung, W.M., Santulli, R.J., Fung-Leung, W.P., Ngo, K., Ye, R.D., Darrow, A.L., Derian, C.K., de Garavilla, L., Andrade-Gordon, P. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  2. Protease-activated receptor-2 activation induces acute lung inflammation by neuropeptide-dependent mechanisms. Su, X., Camerer, E., Hamilton, J.R., Coughlin, S.R., Matthay, M.A. J. Immunol. (2005) [Pubmed]
  3. Deficiency of PAR-2 gene increases acute focal ischemic brain injury. Jin, G., Hayashi, T., Kawagoe, J., Takizawa, T., Nagata, T., Nagano, I., Syoji, M., Abe, K. J. Cereb. Blood Flow Metab. (2005) [Pubmed]
  4. Down-regulation of trypsinogen expression is associated with growth retardation in {alpha}1,6-fucosyltransferase-deficient mice: attenuation of proteinase-activated receptor 2 activity. Li, W., Nakagawa, T., Koyama, N., Wang, X., Jin, J., Mizuno-Horikawa, Y., Gu, J., Miyoshi, E., Kato, I., Honke, K., Taniguchi, N., Kondo, A. Glycobiology (2006) [Pubmed]
  5. Protease-activated receptor-2 augments experimental crescentic glomerulonephritis. Moussa, L., Apostolopoulos, J., Davenport, P., Tchongue, J., Tipping, P.G. Am. J. Pathol. (2007) [Pubmed]
  6. Neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal death in a mouse model of antiphospholipid syndrome. Redecha, P., Franzke, C.W., Ruf, W., Mackman, N., Girardi, G. J. Clin. Invest. (2008) [Pubmed]
  7. Protease-activated receptor-2 exerts contrasting model-specific effects on acute experimental pancreatitis. Laukkarinen, J.M., Weiss, E.R., van Acker, G.J., Steer, M.L., Perides, G. J. Biol. Chem. (2008) [Pubmed]
  8. Proteinase-activated receptor-2 and hyperalgesia: A novel pain pathway. Vergnolle, N., Bunnett, N.W., Sharkey, K.A., Brussee, V., Compton, S.J., Grady, E.F., Cirino, G., Gerard, N., Basbaum, A.I., Andrade-Gordon, P., Hollenberg, M.D., Wallace, J.L. Nat. Med. (2001) [Pubmed]
  9. Essential role for proteinase-activated receptor-2 in arthritis. Ferrell, W.R., Lockhart, J.C., Kelso, E.B., Dunning, L., Plevin, R., Meek, S.E., Smith, A.J., Hunter, G.D., McLean, J.S., McGarry, F., Ramage, R., Jiang, L., Kanke, T., Kawagoe, J. J. Clin. Invest. (2003) [Pubmed]
  10. A major role for proteolytic activity and proteinase-activated receptor-2 in the pathogenesis of infectious colitis. Hansen, K.K., Sherman, P.M., Cellars, L., Andrade-Gordon, P., Pan, Z., Baruch, A., Wallace, J.L., Hollenberg, M.D., Vergnolle, N. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  11. Protection against acute pancreatitis by activation of protease-activated receptor-2. Sharma, A., Tao, X., Gopal, A., Ligon, B., Andrade-Gordon, P., Steer, M.L., Perides, G. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  12. Role of N-methyl-D-aspartate receptors and the nitric oxide pathway in nociception/hyperalgesia elicited by protease-activated receptor-2 activation in mice and rats. Kawabata, A., Kawao, N., Itoh, H., Shimada, C., Takebe, K., Kuroda, R., Masuko, T., Kataoka, K., Ogawa, S. Neurosci. Lett. (2002) [Pubmed]
  13. Effect of protease-activated receptor-2 deficiency on allergic dermatitis in the mouse ear. Kawagoe, J., Takizawa, T., Matsumoto, J., Tamiya, M., Meek, S.E., Smith, A.J., Hunter, G.D., Plevin, R., Saito, N., Kanke, T., Fujii, M., Wada, Y. Jpn. J. Pharmacol. (2002) [Pubmed]
  14. Cockroach allergen extract stimulates protease-activated receptor-2 (PAR-2) expressed in mouse lung fibroblast. Kondo, S., Helin, H., Shichijo, M., Bacon, K.B. Inflamm. Res. (2004) [Pubmed]
  15. PAR-2 agonists induce contraction of murine small intestine through neurokinin receptors. Zhao, A., Shea-Donohue, T. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  16. Genetic evidence that protease-activated receptors mediate factor Xa signaling in endothelial cells. Camerer, E., Kataoka, H., Kahn, M., Lease, K., Coughlin, S.R. J. Biol. Chem. (2002) [Pubmed]
  17. Protease-activated receptor-2 mediates proliferative responses in skeletal myoblasts. Chinni, C., de Niese, M.R., Jenkins, A.L., Pike, R.N., Bottomley, S.P., Mackie, E.J. J. Cell. Sci. (2000) [Pubmed]
  18. Abrogation of bronchial eosinophilic inflammation and attenuated eotaxin content in protease-activated receptor 2-deficient mice. Takizawa, T., Tamiya, M., Hara, T., Matsumoto, J., Saito, N., Kanke, T., Kawagoe, J., Hattori, Y. J. Pharmacol. Sci. (2005) [Pubmed]
  19. Protease-activated receptor-2 peptides activate neurokinin-1 receptors in the mouse isolated trachea. Abey, H.T., Fairlie, D.P., Moffatt, J.D., Balzary, R.W., Cocks, T.M. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  20. Protease-activated receptors mediate apamin-sensitive relaxation of mouse and guinea pig gastrointestinal smooth muscle. Cocks, T.M., Sozzi, V., Moffatt, J.D., Selemidis, S. Gastroenterology (1999) [Pubmed]
  21. Protease-activated receptor 2 mediates the proinflammatory effects of synovial mast cells. Palmer, H.S., Kelso, E.B., Lockhart, J.C., Sommerhoff, C.P., Plevin, R., Goh, F.G., Ferrell, W.R. Arthritis Rheum. (2007) [Pubmed]
  22. Stimulation of protease-activated receptor-2 inhibits airway eosinophilia, hyperresponsiveness and bronchoconstriction in a murine model of allergic inflammation. De Campo, B.A., Henry, P.J. Br. J. Pharmacol. (2005) [Pubmed]
  23. Agonist recognition by proteinase-activated receptor 2 and thrombin receptor. Importance of extracellular loop interactions for receptor function. Lerner, D.J., Chen, M., Tram, T., Coughlin, S.R. J. Biol. Chem. (1996) [Pubmed]
  24. Protease-activated receptor-2 activating peptide SLIGRL inhibits bacterial lipopolysaccharide-induced recruitment of polymorphonuclear leukocytes into the airways of mice. Moffatt, J.D., Jeffrey, K.L., Cocks, T.M. Am. J. Respir. Cell Mol. Biol. (2002) [Pubmed]
  25. Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Camerer, E., Qazi, A.A., Duong, D.N., Cornelissen, I., Advincula, R., Coughlin, S.R. Blood (2004) [Pubmed]
  26. Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa. Camerer, E., Huang, W., Coughlin, S.R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  27. Involvement of neutrophil recruitment and protease-activated receptor 2 activation in the induction of IL-18 in mice. Ikawa, K., Nishioka, T., Yu, Z., Sugawara, Y., Kawagoe, J., Takizawa, T., Primo, V., Nikolic, B., Kuroishi, T., Sasano, T., Shimauchi, H., Takada, H., Endo, Y., Sugawara, S. J. Leukoc. Biol. (2005) [Pubmed]
  28. Protein-tyrosine phosphatase SHP2 is positively linked to proteinase-activated receptor 2-mediated mitogenic pathway. Yu, Z., Ahmad, S., Schwartz, J.L., Banville, D., Shen, S.H. J. Biol. Chem. (1997) [Pubmed]
  29. Protease-activated receptor-2 simultaneously directs beta-arrestin-1-dependent inhibition and Galphaq-dependent activation of phosphatidylinositol 3-kinase. Wang, P., DeFea, K.A. Biochemistry (2006) [Pubmed]
  30. Activation of protease-activated receptor-2 leads to inhibition of osteoclast differentiation. Smith, R., Ransjö, M., Tatarczuch, L., Song, S.J., Pagel, C., Morrison, J.R., Pike, R.N., Mackie, E.J. J. Bone Miner. Res. (2004) [Pubmed]
  31. Basolateral proteinase-activated receptor (PAR-2) induces chloride secretion in M-1 mouse renal cortical collecting duct cells. Bertog, M., Letz, B., Kong, W., Steinhoff, M., Higgins, M.A., Bielfeld-Ackermann, A., Frömter, E., Bunnett, N.W., Korbmacher, C. J. Physiol. (Lond.) (1999) [Pubmed]
 
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